The purpose of this study is to evaluate the 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.

Inclusion Criteria:

• The subject has radiographic evidence of progressive or recurrent GBM by MRI scan (performed within the past 14 days and while on a fixed or decreasing dose of steroids for at least 5 days), and in first or second relapse.
• Subjects having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: At least 2 weeks since surgery and the subject has recovered from the effects of surgery (residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a baseline MRI should be done within 14 days before the first dose of XL184. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable or decreasing steroid dose for at least 5 days).
• The subject is at least 18 years old.
• The subject has a KPS (Karnofsky Performance Scale) of ≥ 60%.
• The subject is capable of understanding the protocol and has signed the informed consent document.
• The subject has adequate organ and marrow function.
• Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study drug.
• Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

• The subject has received anticancer therapy within 28 days of nitrosoureas or mitomycin C within 42 days, a small molecule kinase inhibitor or non-cytotoxic hormonal agent within 7 days or 5 half-lives of the drug or active metabolites, another investigational agent within 28 days, radiation therapy within 42 days of the first scheduled dose of XL184.
• The subject has received more than two prior antitumor therapies, including initial treatment and treatment for one prior relapse.
• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan.
• The subject is unable to undergo MRI scan (eg, has pacemaker).
• The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before the first dose of XL184 (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• The subject has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered before study enrollment.
• The subject is pregnant or breast-feeding.
• The subject has an infection requiring systemic treatment.
• The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulation.
• The subject has serious intercurrent illness, such as uncontrolled hypertension, unhealed wounds from recent surgery or cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within the past 3 months or myocardial infarction within the past 6 months.
• The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed > 5 years ago and has no evidence of disease for 5 years before screening for this study).